title: Prodrug strategies for improved efficacy of nucleoside antiviral inhibitors.
abstract: OBJECTIVE
  This review focuses on the chemical and pharmacological rationale behind the development of nucleoside antiviral prodrugs (NAPs).
  
  
  RESULTS
  Highly efficacious NAPs have been developed that extend and improve the quality of lives of individuals infected with HIV and hepatitis B virus (HBV), herpes viruses, and adenovirus infection in immunocompromised individuals. A very high rate of hepatitis C virus (HCV) cure is now possible using NAPs combined with other direct acting antiviral agents (DAAs).
  
  
  CONCLUSIONS
  Prodrug strategies can address the issues of poor oral bioavailability and delivery of active metabolites to the targeted cells. Additionally, NAPs demonstrate potential for improving deficiencies in oral absorption, metabolism, tissue distribution, cellular accumulation, phosphorylation, and overall potency, in addition to diminishing potential for in-vivo selection of resistant viruses. NAPs continue to be the backbone for the treatment of HIV and HBV, herpesviruses, and adenovirus infections because their active forms are potent, have long intracellular half-lives and are relatively safe with high barrier to resistance.
authors.affiliation: aLaboratory of Biochemical Pharmacology, Department of Pediatrics, Center for AIDS Research, Emory University School of Medicine, Atlanta, Georgia, USA bVeterans Affairs Medical Center, Decatur, Georgia, USA.
authors.forename: Selwyn J
authors.initials: SJ
authors.lastname: Hurwitz
authors.forename: Raymond F
authors.initials: RF
authors.lastname: Schinazi
mesh_terms: D000998:Antiviral Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology*; D006801:Humans; D009705:Nucleosides / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology*; D011355:Prodrugs / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology*; D014777:Virus Diseases / Q000188:drug therapy*
chemical_list: D000998:Antiviral Agents; D009705:Nucleosides; D011355:Prodrugs